Marmorstein, Alan D.

Abstract Human fibrin hydrogels are a popular choice for use as a biomaterial within tissue engineered constructs because they are biocompatible, nonxenogenic, autologous use compatible, and biodegradable. We have recently demonstrated the ability to culture induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium on fibrin hydrogels. However, iPSCs themselves have relatively few substrate options (e.g., laminin) for expansion in adherent cell culture for use in cell therapy. To address this, we investigated the potential of culturing iPSCs on fibrin hydrogels for three-dimensional applications and further examined the use of fibrinogen, the soluble precursor protein, as a coating substrate for traditional adherent cell culture. iPSCs successfully adhered to and proliferated on fibrin hydrogels. The two-dimensional culture with fibrinogen allows for immediate adaption of culture models to a nonxenogeneic model. Similarly, multiple commercially available iPSC lines adhered to and proliferated on fibrinogen coated surfaces. iPSCs cultured on fibrinogen expressed similar levels of the pluripotent stem cell markers SSea4 (98.7% ± 1.8%), Oct3/4 (97.3% ± 3.8%), TRA1-60 (92.2% ± 5.3%), and NANOG (96.0% ± 3.9%) compared with iPSCs on Geltrex. Using a trilineage differentiation assay, we found no difference in the ability of iPSCs grown on fibrinogen or Geltrex to differentiate to endoderm, mesoderm, or ectoderm. Finally, we demonstrated the ability to differentiate iPSCs to endothelial cells using only fibrinogen coated plates. On the basis of these data, we conclude that human fibrinogen provides a readily available and inexpensive alternative to laminin-based products for the growth, expansion, and differentiation of iPSCs for use in research and clinical cell therapy applications. Stem Cells Translational Medicine 2019;8:512–521

Purpose: To report a case of adult-onset vitelliform macular dystrophy in a patient who was found to have a previously unreported variant of the IMPG2 gene. Methods: Case report. Results: A 65-year-old white woman with no significant medical or ocular history presented with a complaint of persistent wavy vision for 10 months. On funduscopic examination, bilateral vitelliform lesions of approximately 1 mm in the right eye and 0.5 mm in the left eye were evident, with no choroidal neovascularization in either eye. The patient was diagnosed with adult-onset vitelliform macular dystrophy. Genetic testing revealed a single likely pathogenic variant of the IMPG2 gene that may explain the examination findings. Conclusion: Adult-onset vitelliform macular dystrophy is a common and relatively benign condition occurring in approximately 1 in 8,000 individuals. Although vitelliform lesions can be a manifestation of systemic diseases or be idiopathic, in a minority of patients, genetic predisposition may play a role. Mutations in four particular genes BEST1, PRPH2, IMPG1, and IMPG2 have been associated with some cases of adult-onset vitelliform macular dystrophy, with this particular gene variant of IMPG2 being previously unreported.